| Autor: |
Buijsen RAM; Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., van der Graaf LM; Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Kuijper EC; Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Pepers BA; Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Daoutsali E; Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Weel L; Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Raz V; Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Parfitt DA; Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., van Roon-Mom WMC; Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands. |
| Abstrakt: |
Antisense technology demonstrates significant potential for addressing inherited brain diseases, with over a dozen products already available and numerous others in the development pipeline. The versatility of differentiating induced pluripotent stem cells (iPSCs) into nearly all neural cell types proves invaluable for comprehending the mechanisms behind neurological diseases, replicating cellular phenotypes, and advancing the testing and development of new therapies, including antisense oligonucleotide therapeutics. While delivering antisense oligonucleotides (ASOs) to human iPSC-based neuronal models has posed challenges, this study explores various delivery methods, including lipid-based transfection, gymnotic uptake, Ca (2+) -enhanced medium (CEM)-based delivery, and electroporation, in 2D and 3D hiPSC-derived neuronal models. This study reveals that CEM-based delivery exhibits efficiency and low toxicity in both 2D neuronal cultures and 3D brain organoids. Furthermore, the findings indicate that CEM is slightly more effective in neurons than in astrocytes, suggesting promising avenues for further exploration and optimization of preclinical ASO strategies in the treatment of neurological disorders. |
